Has the FDA stacked the deck in Avandia’s favor?

Has the FDA stacked the deck in Avandia’s favor?

It didn’t take long for the feeding frenzy to begin once the FDA posted the documents for the upcoming meeting on Avandia. As anticipated the main stream media picked up on the story with the general slant being that Avandia should be pulled from the market and that GlaxoSmithKline (NYSE:GSK) acted improperly, possibly illegally.

While it’s difficult to wade through all of the documentation posted by the FDA, perhaps the most critical document is the two page questions to the committee. Of the nine questions, question number 8 is the most critical as it asks;

“Based on the available data, which of the following regulatory actions do you recommend FDA pursue regarding rosiglitazone? Please select only one option or if you wish to abstain, do not vote. (These options are listed from the most favorable to rosiglitazone to least favorable to rosiglitazone and do not reflect any prejudgment on part of FDA,)

A.     Allow continued marketing and revise the current label to remove the boxed warning and other warnings regarding an increase risk of ischemic CV events, or

B.     Allow continued marketing and make no changes to the current label, or

C.     Allow continued marketing and revise the current label to add additional warnings (e.g., contraindications for certain patient populations, recommendation for second-line use in patients intolerant of or uncontrolled on other anti-diabetic agents); or

D.     Allow continued marketing, revise the current label to add additional warnings, and add additional restrictions on use (such as restricting prescribing to certain physicians or requiring special physician and patient education)

E.      Withdrawal from the U.S. market”

Looking over the question and possible answer selection a few points should be noted;

1.      Of the five possible answers four allow Avandia to remain on the market.

2.      With 33 voting members it’s quite possible, even likely that no one answer will receive a clear majority

3.      What does the FDA do if there is a split vote?

4.      Has the FDA by the very design of this question only added to the controversy?

5.      Is not the issue of this whole meeting to decide whether or not Avandia remains on the US market why not ask two different questions – first whether or not Avandia should remain on the market and then if the panel votes yes – what changes, if any, need to made if Avandia is allowed to remain on the market. Taking this approach would have provided a much clearer choice and would have likely avoided the inevitable confusion that will follow after the committee splits the vote.

Only the FDA can write a question that adds to confusion when clarity is needed.

One could argue that if the committee votes in favor of withdrawal given the other possible options that will send a clear signal. This assumes of course that the vote is clear majority and not a narrow majority. While Diabetic Investor is not an expert in mathematics even rudimentary math skills indicate there is a strong possibility that no one answer will receive a clear majority. And where will that leave everyone? Right back where we started and all this time and effort would be wasted.

The reality is looking over all the data any member of the committee can find enough evidence to keep Avandia on the market. Unlike a criminal trial there is no smoking gun that proves beyond a reasonable doubt that Avandia is guilty as charged.

Diabetic Investor also finds it quite interesting that five voting members of the committee carry with them an expertise in biostatistics. This is not that surprising given that there will be much debate over the use of meta-analysis, which studies were included in the meta-analysis and how to interrupt all this data. As Diabetic Investor noted before because of the use of meta-analysis which opens the door for different conclusions from the same data sets, it’s next to impossible to definitively prove Avandia guilty.

The bottom line here is that the more Diabetic Investor looks over all the data, the make-up of the committee and the questions they are being asked to answer the more obvious it becomes that nothing substantive will come out of this meeting and when it’s over everyone will be asking the same question that started this whole mess; is Avandia safe and should it remain on the market. Perhaps this is the result the FDA wanted all along, they certainly stacked the deck to make it look this way.